Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG.sub.2, PGH.sub.2 and PGE.sub.2, has been a common target of anti-inflammatory drug discovery. However, common non-steroidal anti-inflammatory drugs (NSAIDs) that are active in reducing the prostaglandin-induced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAIDs can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAIDs is the use of corticosteroids, which have even more drastic side effects, especially when long term therapy is involved.
Previous NSAIDs have been found to prevent the production of prostaglandins by inhibiting enzymes in the human arachidonic acid/prostaglandin pathway, including the enzyme cyclooxygenase (COX). The recent discovery of an inducible enzyme associated with inflammation (named "cyclooxygenase II (COX II)" or "prostaglandin G/H synthase II") provides a viable target of inhibition which more effectively reduces inflammation and produces fewer and less drastic side effects.
Pyrazole compounds have been used in the treatment of inflammation. U.S. Pat. No. 5,134,142 to Matsuo et al describes 1,5-diaryl pyrazoles, and more particularly, 1-(4-fluorophenyl)-5-4-(methylsulfonyl)phenyl!-3-(5-tetrazolyl)pyrazole, as having anti-inflammatory activity.
U.S. Pat. No. 4,146,721 to Rainer describes 1,3,5-triphenyl pyrazoles as useful analgesics, anti-inflammatory agents and antipyretics, and specifically describes 1,3,5-triphenyl-pyrazol-4-acetamide.
U.S. Pat. No. 3,254,093 to Huisgen et al describes a process for preparing pyrazoles, including ethyl-1,3,5-triphenyl-1H-pyrazole-4-carboxylate.
The synthesis of a series of 3-phenyl-5-(2-phenyltriazol-4-yl)!-1H-pyrazol-1-yl!benzenesulfonamides is described H. Faidallah et al, Pak. J. Sci. Ind. Res., 35, 213 (1992)!, and specifically 4-4-bromo-3-(4-methylphenyl)-5-(2-phenyl-2H-1,2,3-triazol-4-yl)-1H-pyrazo l-1-yl!benzenesulfonamide. The synthesis of a series of related triazole substituted pyrazolyl benzenesulfonamides has been described H. Mokhtar et al, Pak. J. Sci. Ind. Res., 35, 428 (1992)!.
The use of 4-3-(4-aminophenyl)-5-phenyl-1H-pyrazol-1-yl!benzenesulfonamide as an intermediate in the synthesis of the corresponding benzenesulfonylureas has been described H. Faid-Allah et al, Ind. J. Chem., 27B, 245 (1988)!. An intermediate for antidiabetic agents, 4-3-phenyl-5-bromophenyl-1H-pyrazol-1-yl!benzenesulfonamide, has been described R. Soliman et al, J. Pharm. Sci., 76, 626 (1987)!. The condensation of sulfamylphenylhydrazines with chalcones to produce 4-3,5-diphenyl-pyrazol-1-yl!benzenesulfonamides has been reported, which are potential hypoglycemic agents H. Faidallah et al, Pak. J. Sci. Ind. Res., 35, 8 (1992)!. Specifically, 4-3,5-bis(4-methoxyphenyl)-1H-pyrazol-1-yl!benzenesulfonamide is described. 4-3,5-Diphenyl-1H-pyrazol-1-yl!benzenesulfonamide has been produced and evaluated for antidiabetic activity R. Soliman et al, J. Pharm. Sci., 70, 606 (1981)!.